Cystic Fibrosis (CF), one of the most frequent hereditary diseases due to mutations in the CFTR gene, causes mortality in humans mainly due to infection in the respiratory system. However, besides the massive inflammatory response triggered by chronic bacterial infections, a constitutive pro-inflammatory state associated with the most common CFTR mutations has been reported in paediatric cases before the onset of bacterial colonization. In previous works we isolated and characterized a mix of virulent bacteriophages (phage cocktail) able to efficiently counteract Pseudomonas aeruginosa infection in a zebrafish model with cftr loss-of-function (LOF), but also showing anti-inflammatory effects in zebrafish embryos not infected by bacteria.

On these premises, in this work we demonstrated the anti-inflammatory role of the phage cocktail both in the wild-type (WT) and hyper-inflamed cftr LOF zebrafish embryos in terms of reduction of pro-inflammatory markers. We also dissect that only the virion proteinaceous components, but not the phage DNA, are responsible for the immune-modulatory effect and that this action is elicited through the activation of the Toll-like Receptor (TLR) pathway. In the cftr LOF zebrafish embryos, we demonstrated that phages injection significantly reduces neutrophil migration following acute inflammatory induction. The elucidation of the molecular interaction between phages and the cells of vertebrate immune system might open new possibility in their manipulation for therapeutic benefits especially in diseases such as cystic fibrosis, characterized by chronic infection and inflammation.

囊性纤维化 (CF) 是由于CFTR基因突变引起的最常见的遗传性疾病之一，主要由于呼吸系统感染导致人类死亡。然而，除了由慢性细菌感染引发的大量炎症反应外，在细菌定植之前，在儿科病例中已经报道了与最常见的CFTR突变相关的组成性促炎状态。在以前的工作中，我们分离并表征了能够有效抵抗斑马鱼模型中的铜绿假单胞菌感染的强毒噬菌体（噬菌体鸡尾酒）混合物。功能丧失（LOF），但在未被细菌感染的斑马鱼胚胎中也显示出抗炎作用。

在这些前提下，在这项工作中，我们证明了噬菌体混合物在减少促炎标志物方面在野生型 (WT) 和过度发炎的cftr LOF 斑马鱼胚胎中的抗炎作用。我们还剖析了只有病毒体蛋白质成分而不是噬菌体 DNA 负责免疫调节作用，并且这种作用是通过激活 Toll 样受体 (TLR) 途径引起的。在cftrLOF 斑马鱼胚胎，我们证明噬菌体注射显着减少急性炎症诱导后的中性粒细胞迁移。阐明噬菌体与脊椎动物免疫系统细胞之间的分子相互作用可能会为它们的治疗带来新的可能性，特别是在以慢性感染和炎症为特征的疾病如囊性纤维化中。